The advance of medical technology has permitted the development of monoclonal antibodies which have been designed with a high degree of affinity for specific cell tissue. These antibodies can be conjugated ("tagged") with radioactive isotopes for the visualization of tissues for which the antibodies are specific. For example, cancer tissue-specific monoclonal antibodies can be conjugated with radioactive isotopes to facilitate imaging of soft tissue turmors which would otherwise be difficult to image with conventional X-ray techniques. In addition, these antibodies can be tagged with radioactive material for the treatment of cancer. This form of chemotherapy is advantageous in that the radioactive material is delivered directly to the site of the tumor through the bloodstream.
Prior to introduction of the above-described site-specific medicine into the human body, the conjugated antibody must be isolated from a reaction solution containing: the desired antibody conjugated with the radioactive material; unbound antibody; unbound radioactive material; and other impurities. Each of these items (other than the desired conjugated antibody) exists as ions in the solution. Thus, the desired, conjugated antibody is typically isolated by passing the reaction solution through an ion-exchange column.
A conventional, prior art, ion-exchange column is identified by reference numeral 10 in FIG. 2. The ion-exchange column has a fluid inlet 12 for introduction of the reaction solution from which the conjugated antibody is to be isolated. The isolated, conjugated antibody exits the ion-exchange column through a fluid outlet 14. The ion-exchange column contains an ion-exchange resin 16 which has an affinity for the anionic, unconjugated radioactive material so as to retain this undesirable material in the ion-exchange column while allowing the uncharged, conjugated antibody to pass therethrough. During this process, other, undesirable anions are retained in the column (during this reaction, the ion-exchange resin gives up a harmless anion, such as chlorine, which exits the fluid outlet 14 with the isolated, conjugated antibody).
The ion-exchange resin 16 typically comprises a polymer material which binds quaternary amino ethyl crystals (such as QAE-Sephadex) together. Prior to introduction of the reaction solution into the fluid inlet 12, the ion-exchange resin 16 is hydrated with a buffer solution. The buffer solution maintains a relatively narrow pH range within the ion-exchange column during passage of the reaction solution therethrough.
Without the buffer solution, the ion-exchange resin was the consistency of a tacky powder. Upon introduction of the buffer solution into the fluid inlet 12, the ion-exchange resin assumes the consistency of a slurry. To prevent the partially liquefied ion-exchange resin from passing through the fluid outlet 14 during operation of the column, and to prevent the tacky, unhydrated ion-exchange resin from falling out the fluid inlet 12 during storage of the ion-exchange column, hard fibrous inserts or "frits" 18, 20 are positioned adjacent to the fluid inlet 12 and fluid outlet 14, respectively.
The insert 20 adjacent to the outlet 14 also traps fine particles which result from degradation of the ion-exchange resin itself. The ion-exchange resin is in the form of a crystalline solid before hydration, and is in the form of a crystalline solid in solution when hydrated. The solid particles of the ion-exchange resin are relatively fragile and swell or contract by osmotic action according to the pH of the buffer solution introduced through the fluid inlet 12. It is highly desirable for all of the solution entering the fluid inlet 12 to fully contact the ion-exchange resin 16 before leaving the fluid outlet 14. Therefore, the ion-exchange resin is relatively tightly packed into the ion-exchange column between the hard inserts 18,20 to minimize the formation of voids and fluid channels in the reaction medium during operation of the ion-exchange column. As a consequence of this tight packaging and the repeated expansion of the crystals against the hard inserts 18, 20, the crystals begin to fracture and form fine particles ("fines"). These "fines" are trapped in the insert 20 and do not exit the fluid outlet 14. The insert 20 may eventually become clogged with these fine particles diminishing the efficacy of the column even though the ion exchange medium remains functional. In addition, undesirable voids are formed in the ion exchange resin when the resin contracts. Therefore, a need exists for a vertical reaction vessel which can accommodate volumetric changes of an ion-exchange resin contained therein.
In addition to the inability of the prior art ion-exchange column to compensate for volumetric changes in the ion-exchange resin, fluid flow distribution irregularities are associated with this device. As shown in FIG. 2, the fluid inlet 12 and fluid outlet 14 are provided with conventional Luer locks 22 and 24, respectively, having internal diameters 26, 28 which are limited by the outer diameter of a standard Luer lock. The diameter 30 and length 32 of a reaction chamber 34 containing the ion-exchange resin 16 are determined by the desired flow rate of the reaction solution through the ion-exchange column.
As is often the case, the diameter 30 of the reaction chamber 34 is significantly larger than the inner diameters 26, 28 of the fluid inlet and outlet to accommodate a desired flow rate through the ion-exchange resin 16. The reaction solution tends to form a conical fluid distribution 36, as shown in FIG. 2, which does not provide a desired, uniform fluid flow across the entire cross-sectional area of the reaction chamber. A uniform fluid flow is necessary to provide a uniform exposure for all of the reaction fluid flowing through the column. In the conical distribution 36 shown in FIG. 2, the fluid on the outside of the conical distribution has a longer travel path through the ion-exchange resin 16 and a greater period of exposure to the ion-exchange resin than does fluid passing through the center of the distribution. In addition, circled areas 38 and 40 of the ion-exchange resin receive little, if any, fluid flow and thus do not react with the reaction solution. Therefore, a need exists for a vertical reaction vessel which promotes a uniform fluid flow throughout the entire cross section of the ion-exchange resin.